What is fluid therapy?

Fluid therapy refers to the administration of fluids, medications, blood and blood products to a patient. These fluids are preferably given orally. However, when the patient cannot take in any fluids orally, intravenous (IV) fluid therapy is used. In IV fluid therapy, the fluids are directly given to the patient in their vein. IV fluid therapy is highly effective in emergency situations such as septic shock and trauma.

Read more: Must-have features in ventilators for severe COVID-19 patients

Normally, fluids make up about 60% of the total body weight in men (about 42 litres in a man who weighs 70 kilograms) and about 52% of total body weight in women (about 28.6 litres in a woman who weighs 55 kilograms).

These fluids consist of water and electrolytes like sodium, potassium and chloride. Water alone makes up about 50% to 70% of total body weight in adults. This water could be present inside (intracellular) or outside (extracellular) body cells and helps in transporting nutrients and minerals in the body. The extracellular water could be present inside vessels (both blood and lymph) or in interstitial spaces (spaces around cells). Sodium and chloride are mostly present outside cells, while potassium is mostly present inside cells.  

In a body with 42 litres of fluid:

• About 28 litres is present as intracellular fluid (40% of body weight)
• About 14 litres as extracellular fluid (20% of body weight). In extracellular fluid:
  • 11 litres (or 15% of body weight in a 70 kg man) is present as interstitial fluid
  • 4 litres (about 5% of body weight) is present as plasma (in the blood)

The volume of blood is about 8% of total body weight (about 5.6 litres in a 70kg man).

Maintainance of fluid-electrolyte balance: 

However, both water intake and release from the body can be sensible (obtained from oral fluids and food and released through urine and faeces and sweat) and insensible (gained through metabolic processes in the body and lost through the lungs and skin). Here is a table explaining the total sensible and insensible water intake and expulsion in a man weighing 70 kg:

A healthy (70Kg) adult needs around 30-35 mL of water per Kg of their body weight per day. The total normal intake would be around 2,500mL/day and total output would be around 1,400-2,300mL/day.

Here is how the water intake is calculated for any weight type:

• For the first 10 Kg: 100mL/Kg of body weight
• For the next 10 Kg: 50mL/Kg of body weight
• For the rest of the weight: 20mL/Kg 

Fluid balance could either be negative or positive:

• Positive fluid balance occurs when fluid intake is greater than fluid output.
• Negative fluid balance occurs when fluid intake is less than fluid output.

The required intake of some electrolytes is as follows:

• Sodium: Under 1,500 milligrams per day (mg/day) in adults. Babies under 12 months should not have more than 400 mg/day of sodium. Infants aged 1-3 years can have up to 800 mg/day of sodium.
• Chloride: 9 mg/day per kilo body weight. So, a man weighing 70 kilos would need 63 mg/day of chloride. Children can have up to 45mg/day of chloride.
• Potassium: Adults need between 3,500mg and 4,700mg of this mineral daily. Children under 3 years of age need about 3,000 mg/day of potassium.
• The other electrolytes present in intracellular and extracellular fluids include calcium, magnesium, HCO3, SO42-, and HPO43-. The fluid also has some proteins. 

Read more: Electrolyte imbalance symptoms, causes, diagnosis, treatment, prevention

The volume of fluid in the body is maintained through various systems. However, antidiuretic hormone (ADH) majorly controls fluid balance in the body. ADH is released by the hypothalamus, a gland present in the brain in response to changes in the osmolality and blood pressure in the body. Osmolality indicates the concentration of solutions - how thick or flowy they are - measured in terms of the number of solutes (the component dissolved in a solution) present in per kg of the solution.

The Renin-angiotensin system (RAS) also helps maintain the fluid-electrolyte balance in the body. It signals the body in response to blood pressure changes in the kidneys so the body can store or release more water and/or electrolytes as needed. 

Read more: What is the role of renin-angiotensin-aldosterone inhibitors in the treatment of COVID-19?

If a person has a severe disease or has an injury, their body will not be able to maintain fluid-electrolyte balance. This is when fluid therapy is needed.

Dehydration is one cause of fluid imbalance. Hyperventilation, fever and raised metabolism increase insensible water loss. Heat/fever above 100.5 degree Celsius can increase insensible water loss by up to 300mL/degree rise/day.

Further, patients who have had a tracheostomy are at greater risk of water loss - especially if it's non-humidified. A tracheostomy is a procedure to create an opening in the windpipe, at the front of the neck, just below the vocal cords so the patient can breathe. It can lead to insensible water loss of more than 1.5 L/day. Tracheostomy collars are used to give oxygen therapy to patients.

Read more: Oxygen therapy for COVID-19

Some of the health conditions that can cause fluid imbalances are:

• Chronic kidney disease: When the kidneys can’t function properly, the body is unable to expel all the extra fluids. This is why chronic kidney disease leads to imbalances in fluids and electrolytes in the body.
• Surgery: After any surgery, the body tends to store a lot of water for a while. As a result, the patient often notices swelling.
• Heart failure: In the case of heart failure, the heart finds it difficult to properly pump blood in the body. This leads to fluid accumulation in body tissues, liver, lungs and blood vessels.
• Throwing up or heavy bleeding: Vomiting or severe blood loss can cause dehydration and imbalance in fluid and electrolytes in the body.
• Lack of ADH, leading to fluid imbalance.   
• Sepsis and septic shock: Sepsis is defined as an overwhelming inflammatory response in the body, to fight an infectious microbe. Inflammation shows up as low blood pressure, fever, increased heartbeat (more than 90 beats per minute) and respiratory rate (more than 20 breaths per minute) and high (more than 12000 cubic mm/mL) or low (less than 4000 cubic mm/mL) white blood cell (WBC) count. Sepsis negatively affects all body organs and may lead to gradual organ failure. When sepsis leads to dangerously low blood pressure, it is called septic shock. In the case of septic shock, the person’s body organs do not get enough blood (and hence oxygen and nutrients) and start to malfunction. Septic shock can be fatal.
• Injuries and burns

Read more: Inflammation and COVID-19

According to an article published in the International Journal of Medical and Health Research, fluid disturbances can be roughly divided into three types: 

1. Changes in the volume of fluid:

• Hypovolemia: Decrease in extracellular fluids in the body, usually blood plasma. This manifests in the form of:
  • Tachycardia (increased heart rate)
  • Dry mucous membranes (inner lining of certain organs like the gut, mouth, nose)
  • Poor skin elasticity
  • Sunken eyes
  • Hypothermia (reduced body temperature)
  • Weight loss
  • Excessive hypovolemia may lead to a condition called hypovolemic shock. There are four stages of hypovolemic shock: ranging from 15% to 40% reduced volume of blood in the body. A person experiencing hypovolemic shock will have reduced peripheral perfusion (compromised delivery of oxygen and nutrients in certain tissues).
    To compensate for hypovolemic shock, the body constricts the blood vessels and increases heart rate, yet the systolic blood pressure may drop to 70 mm of mercury (mmHg) in stage 4. Systolic blood pressure is the pressure with which the heart pumps the blood to the entire body - it is the top number in the blood pressure machine reading. In a healthy individual, systolic blood pressure is in the range of 90-120mmHg.
    This results in a reduction in oxygen delivery to important organs and a condition called lactic acidosis. If left untreated, hypovolemic shock can lead to organ damage and organ failure and death. This is because the body tries to divert blood flow to heart and brain instead of other organs.
• Hypervolemia: Fluid overload or the presence of excess fluids in the body. Hypervolemia shows up as: 
  • Shortness of breath
  • Weight gain
  • Pitting oedema: Swollen areas which form a depression or pits when you press against the skin.
  • Ascites: A buildup of fluid in the abdomen.
  • Hepatojugular reflex: Distension of veins in the neck.

2. Changes in the concentration of fluids

• Hyponatremia: It refers to a decrease in sodium concentration in fluids. Hyponatremia occurs when the blood sodium levels drop below 135 milliequivalents per litre (mEq/L). Hyponatremia may occur due to hypovolemia (reduction in total water and sodium levels) or hypervolemia (an increase of total body water compared to sodium) or euvolemic (increase in total body water and normal sodium levels). Some signs of hyponatremia include:
  • Headache
  • Stupor
  • Confusion
  • Fits
  • Coma
• Hypernatremia: Hypernatremia refers to an increase in sodium concentration in the body. (Read more: Sodium test)
  Patients show symptoms of fluid and water loss or signs of:
  • Dehydration
  • Increased thirst
  • Dry or velvety skin
  • Children may be irritable and tend to cry easily.
  • Brain haemorrhage is a serious complication of hypernatremia

3. Changes in composition: This includes changes in the concentration of electrolytes in the body fluids and acid-base imbalances. 

Read more: Causes of death in COVID-19 patients

There are various indications that determine if a patient needs fluid therapy. These include:

• Weight of the person: An increase in weight indicates fluid gain and decreased weight can indicate fluid loss. However, to check weight changes, it is best to use a single weighing machine since there is a chance of errors on using different machines.  
• Increased heart rate (Tachycardia): Occurs due to hypovolemia. Tachycardia can be an important indication of hypovolemic shock. But increased heart rate could also be due to fever, anxiety or pain.
• Drop or rise in blood pressure:  Low blood pressure may be an indication of hypovolemia and high blood pressure may occur in hypervolemia. Orthostatic blood pressure is a condition in which a person gets a reduction of about 20mmHg in systolic blood pressure and 10 mm Hg in diastolic blood pressure on standing for a while (2-5 minutes) after lying in a supine position. This is usually seen in the elderly and dehydrated patients.
• Increased respiratory rate: This could also be a sign of hypovolemic shock - it occurs when the body tries to compensate for low oxygen in tissues and metabolic acidosis by breathing more rapidly. The average grown-up takes 12-20 breaths every minute. Increased breathing, at the rate of 30 or more breaths a minute, is a sign that should never be ignored.
• Increased urination: More than 1mL/Kg/hour in adults more than 1.5mL/Kg/hour in children. If the patient is given medications that have a toxic side effect on the kidneys, the urine output would be even more to prevent renal toxicity.
• Capillary refill time of more than 2 seconds: Capillary refill time is the time taken by capillaries to refill with blood after pressure is applied to it. Usually, the capillary refill time is about 2 seconds. However, it may vary with age, ambient light, body temperature, the amount and location of pressure applied. Capillary refill time is easy to test on fingertips and toes.

Laboratory tests

The following tests can be used to evaluate fluid disturbances:

• Blood urea nitrogen and creatinine test: Reduced intravascular (extracellular) fluid volume could result in reduced blood flow to the kidneys (renal blood flow). This, in turn, could cause an increase in blood urea nitrogen or creatinine levels. These can easily be measured through a kidney function test.
• Liver function test: High levels of two enzymes - alanine aminotransferase and aspartate aminotransferase - in the blood could indicate a liver problem. This could happen due to reduced blood flow to the liver (perfusion of the liver). Read more: What is a liver function test?)
• Hematocrit levels: High hematocrit levels due to low blood fluids as compared to red blood cells (RBCs).
• Serum electrolytes: This test can help assess if there is an electrolyte imbalance in the patient’s body and which electrolyte is out of balance. (Read more: Serum osmolality test)

There are two types of fluids used in intravenous fluid therapy:

1. Colloid solutions: Colloidal solutions contain large-sized molecules that cannot go inside cells. These solutions are mainly used to increase extracellular (intravascular) fluid volume. Some examples of colloidal solutions include:

• Albumin
• Gelatin
• Dextran
• Proteins or complex polysaccharides

Colloids are generally more expensive than crystalloids and are associated with a higher risk of side effects - allergy, for example. Colloids are given when crystalloids cannot improve the symptoms of shock in a patient.

2. Crystalloid solutions: Crystalloid solutions, on the other hand, have small molecules that can easily permeate cells and hence can be used to increase intracellular fluid volume. They can also increase fluid volume in intravascular and interstitial spaces. Some crystalloid solutions are that of electrolytes and dextrose that easily get dissolved in water. There are three types of crystalloid solutions:

• Hypotonic solutions: These fluids have low osmolality. So, when a patient gets a hypotonic solution, the water in their extracellular fluid becomes more than that of intracellular and interstitial fluid. As mentioned earlier, water rushes to the area where there are more solutes or less water - in this case inside the cells and interstitial spaces. Hypotonic solutions may cause cells to swell up. While giving hypotonic solutions, patients are constantly monitored for possible hypovolemia (as the water moves from the blood vessels to the cells, it may cause the volume of fluid in the veins to drop). These fluids are not given in case of cerebral oedema, as they may increase the swelling. Some examples of hypotonic solutions include: 
  • 0.33% sodium chloride
  • 0.45% sodium chloride 
  • 0.2% sodium chloride
  • 2.5% dextrose in water     
• Isotonic solutions: The osmolality of an isotonic solution is the same as plasma (iso - same and tonic - tonicity). So, the administration of isotonic solution will not make the water travel on either side of the cell. These solutions are usually used in blood transfusion or transfusion of blood products or for treating dehydration, shock, diarrhoea and metabolic acidosis.

  While giving isotonic solutions to a patient, constant monitoring is done for possible hypovolemic shock. Lactate ringer’s solution has potassium, so it is not given to patients with hyperkalemia (high potassium levels). Also, Ringer’s lactate has calcium which may lead to blood coagulation so in case this solution is being given, and the patient also needs a blood transfusion, separate IV is set for both. Some of the isotonic solutions used in fluid therapy are:

  • Normal saline - 0.9% sodium chloride (NaCl)
  • 5% dextrose in water (D5W)
  • Ringer’s solution
  • Lactated Ringer’s solution
• Hypertonic solution: These solutions have a higher concentration of solutes than blood plasma. As a result, when the patient gets a hypertonic solution through IV, it pulls water from the intracellular spaces into the intravascular spaces.
  Hypertonic solutions are associated with a lot of risks. These solutions are not given in most clinical settings except in the case of hyponatremia. However, even then, the dosage and concentration are adjusted so the condition gets corrected slowly. Sudden correction of sodium levels may lead to a neurological condition called central pontine myelinolysis. It is characterized by damage of the outer sheath of brain cells or the cells themselves, especially in pons, an area in the brain stem.
  Hypertonic solutions are not given to dehydrated patients, especially those with heart failure or kidney failure. Some examples of hypertonic solutions include:
  • 3% sodium chloride
  • D10W, and D5W 
  • 0.45% sodium chloride 

All crystalloid solutions that contain dextrose are not given to patients with hyperglycemia (high blood sugar levels).

Fluid therapy is given for four main reasons:

• Resuscitation
• Maintenance of body fluids 
• Fluid replacement
• Carrying medicines and nutrients

The four D's of fluid therapy

The four D's are drug, duration, dosing, and de-escalation. Before choosing a fluid therapy, all these factors need to be determined:

• What types of fluids need to be given, is it colloids or crystalloids?
• Would the fluids be given through IV or orally?
• Would they be synthetic or blood-derived?
• For how long would the therapy be necessary?
• What would be the composition of the fluid?

Here are the various types of fluids:

• Resuscitation fluids: These fluids are given to improve hypervolemia. In case of septic shock, crystalloid solutions are given as resuscitation fluids. However, rapid administration of fluids may harm the cell membranes which are already weakened by inflammation occurring in trauma or sepsis.
• Maintainance fluids: These fluids are given so that the patient is able to balance their daily requirements of fluids and electrolytes. Maintainance fluids have 20-30 mL/Kg/day of water, 1 millimole/Kg/day of sodium, potassium and chloride, and 50-100/day glucose.
  The delivery pumps for fluid therapy work on an hourly basis. So, the 24-hour volume of total fluid to be given is obtained by dividing the total fluid intake needed for a person into hours. A 4-2-1 formula is used for it. Here is how:
  • 100mL/24 hours = 4mL/Kg/hour for the first 10 Kg of body weight
  • 50mL/24 hours = 2mL/Kg/hour for the second 10 Kg of body weight
  • 20mL/24 hours = 1mL/Kg/hour for the rest of the body weight
• Replacement fluids: These fluids are usually given to compensate for fluids that the patient has lost but cannot take in orally. This may be needed for ongoing fluid losses like through an open wound or due to high body temperature or polyurea.
  These fluids have the same composition as the fluids lost.
• Nutrition fluids: This includes nutrition that is given through the parenteral route - that is through intramuscular injection, subcutaneously (under the skin) or intravenously - in patients who can’t eat yet; such as chronically ill patients. Proper dosing, caloric requirements, etc., are also determined for these fluids.

Fluid resuscitation

Fluid resuscitation has four stages: 

• Rescue
• Optimisation
• Stabilization 
• De-escalation

The patient goes through all these stages as their illness reduces gradually. Here is what happens in the four phases:

• Rescue: This is the first phase of resuscitation that is done to save the life of a person in shock. In this stage, the patient is given fluid bolus therapy - which is the rapid infusion of fluids to reduce hypotension in shock patients. In fluid bolus therapy, the patient is given about 500 mL of fluid within a maximum of 15 minutes. 
• Optimisation: In this stage, the patient is still unstable but is no longer in a life-threatening situation. Fluid therapy in the optimization stage is given a bit more carefully. The main goal of this step is to improve cardiac function to increase tissue perfusion and minimise organ damage. This stage lasts for hours rather than minutes. Instead of fluid boluses, fluid challenge is used in this stage. In fluid challenge, 100-200 mL of fluid is given over 5-10 minutes. After this time, the doctor reassesses the patient’s situation to optimise the tissue perfusion levels. This is done to make sure that there is no fluid overload or hypervolemia. The percentage of fluid overload is calculated by the following formula: total daily fluid intake - total fluid output/ baseline body weight (Kg) X 100
  A 10% fluid overload is associated with harmful effects. Optimisation fluid therapy is given to patients during operations, diabetic ketoacidosis and burns patients. 
• Stabilisation: This stage begins when the patient is stabilised. The fluid therapy in this stage is done to maintain fluid levels in the body; to balance any ongoing fluid losses through normal body processes (sensible and insensible). Fluid infusion is given in case the person is still having major fluid losses for some reason like an underlying health condition. Fluid infusion refers to continuous administration of fluids to maintain normal body processes and balance any fluid loss. The aim of fluid therapy in this stage is to bring the fluid balance to zero or negative. This stage may go on for days.
  Fluid maintenance is kept to a minimum if the person is otherwise not able to take fluids orally. The fluid administration is titrated as per the individual's needs but it is usually not more than 1-2 mL/Kg/hour. Stabilisation fluid resuscitation is given to post-operative patients, and drip and suck management of pancreatitis patients.
• De-escalation: In this stage, IV fluids are removed from the patient who is now recovering. Instead, they are given oral fluids, if needed. The goal of this stage is to attain a negative fluid balance. This may take days to weeks.

According to the National Institute for Health and Care Excellence, UK, the following signs indicate that the patient needs fluid resuscitation:

• Breathing rate greater than 20 breaths per minute
• Systolic blood pressure of less than 100 mm Hg
• Capillary refill time of greater than 2 seconds or a sensation of cold on touching the peripheral body
• Heart rate greater than 90 beats per minute

An IV or fluid therapy can be given in any of the following ways:

1. Peripheral IV: For this, a catheter is placed in a peripheral vein - like that of the hands and arms - and the site is covered with a transparent dressing to keep it from getting infected. The IV is inserted for a short period of up to a week - and needs to be changed every three to four days to avoid infection.

Some of the possible complications of peripheral IVs include:

• Infection at the catheter site which may lead to bacteremia (presence of bacteria in the blood) and sepsis. However, this can be prevented by careful administration of the catheter. 
• Bleeding from the catheter site.
• Phlebitis, which occurs due to irritation of the vein and inflammation of the inner lining of the vein due to the catheter.
• Infiltration or extravasation: Occurs when fluids or medications respectively enter into the surrounding tissue of the catheter. Infiltration may cause pain and swelling of the tissue while extravasation may also cause a burning sensation along with necrosis of the tissue.
• Air embolism: This occurs when air enters into the venous system. This happens when the catheter is removed and shows up as shortness of breath, shoulder and neck pain, lightheadedness, persistent coughing and increased heart rate.
• Catheter embolism - occurs due to breaking of a piece of the catheter in the vein 

2. Central venous catheters (CVCs)

These catheters are placed in one of the large veins in the central circulatory system so that the catheter’s tip ends up in the superior vena cava - the big vein that brings blood to the heart from the upper portions of the body. Unlike peripheral IVs, central venous catheters may need surgery for insertion. These catheters can be kept in for up to a year. A lot of ICU patients have this kind of catheter.

Read more: ICU for COVID-19 patients

These catheters are given to introduce anticancer drugs, multiple medications or toxic mediations, and total parenteral nutrition, among others.

CVCs need special maintenance since they are placed in big veins. These can be inserted through the jugular vein, or subclavian vein (percutaneous CVC), through the upper arm (peripherally inserted CVC), or subcutaneously under the chest area (subcutaneous or tunnelled CVC). A port-a-cath catheter is implanted inside the body cavity and is attached to a port inside the skin.

Some of the risks associated with CVCs are as follows:

• Infection at the site of insertion of the catheter.
• Formation of blood clots in the arms due to the catheter. If this clot travels to the lungs it can lead to pulmonary embolism.
• The catheter may move from its original location.
• Wrong placement of the catheter, which may cause internal bleeding, accumulation of blood in the pleural cavity and cardiac arrest.
• Entry of air into the veins.
• Cracks or tears in the CVC line.

As per the Ministry of Health and Family Welfare guidelines, conservative fluid management should be given to COVID-19 patients with severe acute respiratory illness or SARI (fever, cough and breathing difficulties) without shock.

Aggressive fluid resuscitation is not advised for these patients, though, as it may worsen the oxygenation in their blood and bodies. This is especially important in geographical locations where mechanical ventilation is not available or where there is limited access to ventilation.

Conservative fluid management is also suggested in patients with acute respiratory distress syndrome (ARDS) without tissue hypoperfusion.

Fluid loading is done in case the person shows signs of septic shock. However, hypotonic crystalloids are not to be used, and the use of gelatin and starches is avoided.

For adults with septic shock, fluid resuscitation is given with 30 mL/Kg of isotonic crystalloids (normal saline and Ringer’s lactate) for the first three hours. 

In children in septic shock, 20 mL/Kg of rapid fluid bolus is recommended with about 40-60 mL/Kg of isotonic crystalloids in the first hour.

If the perfusion seems to be working, the need for additional fluid boluses is determined and is given as 250-1000 mL in adults or 10-20 mL/kg in children.

The perfusion targets include:

• Mean arterial pressure greater than 65 mmHg or whatever the appropriate target is as per the patient’s age. 
• Improvement in the patient’s consciousness levels
• Improvement in capillary refill
• Improvement in skin mottling
• Urine output greater than 0.5 mL/Kg/hour in adults or 1mL/Kg/hour in children

However, in the case of shock, fluid resuscitation may lead to volume overload and respiratory failure. If signs of fluid overload show up, fluid resuscitation should be stopped.

Vasopressors - drugs that constrict the blood vessels and cause an increase in blood pressure - can be given during or after fluid management to achieve the blood pressure required. Vasopressors are given through a central venous catheter. However, in the absence of a central venous catheter, an IV line connected to a big vein can be used.

Read more: Intensive care for severely ill COVID-19 patients